晚育:年長(zhǎng)的男人能生健康的孩子嗎?

晚育:年長(zhǎng)的男人能生健康的孩子嗎?

An 86-year-old man recently walked into my office – and wanted to achieve pregnancy using his sperm, donor eggs and a gestational surrogate. He preferred to transfer the embryos to two surrogates because he was well aware of the risks related to twins; however, he had no doubt his sperm could create healthy children at his age. "Charlie Chaplin was a father at the age of 73," he remarked. "Why can't I be a father?" After my patient left, a quick online search revealed that, indeed, the world's most famous older fathers include Mick Jagger and Charlie Chaplin.It raises the questions: When does paternity end, and can older men have healthy children?

最近，一位86歲的老人走進(jìn)我的辦公室，他想用自己的精子、捐贈(zèng)的卵子和代孕媽媽來(lái)懷孕。他更愿意將胚胎移植給兩個(gè)代孕者，因?yàn)樗芮宄p胞胎的風(fēng)險(xiǎn);然而，他毫不懷疑他的精子能在他這個(gè)年齡生出健康的孩子。他說(shuō):“查理·卓別林是一位73歲的父親。“為什么我不能做一個(gè)父親?”在我的病人離開(kāi)后，我快速上網(wǎng)查詢顯示，事實(shí)上，世界上最著名的年長(zhǎng)父親包括米克·賈格爾(Mick Jagger)和查理·卓別林(Charlie Chaplin)。這就提出了一個(gè)問(wèn)題:親子關(guān)系什么時(shí)候結(jié)束?年齡較大的男性能否擁有健康的孩子?

The average age of a father in the U.S. is 30. Most of the prospective fathers who come to my fertility clinic are around age 40. In modern times, we delay maternity and paternity. At age 43, a woman is told 90% of her embryos will be genetically abnormal, while a 68-year-old man is told everything is OK on his side because he has a normal semen analysis. But what happens to the DNA of the sperm as men age?

美國(guó)父親的平均年齡為30歲。大多數(shù)來(lái)我生育診所的準(zhǔn)爸爸都在40歲左右。在現(xiàn)代，我們推遲了生育和親子關(guān)系。43歲的女性被告知90%的胚胎在基因上是不正常的，而68歲的男性則被告知一切正常，因?yàn)樗木悍治稣?。但是隨著男性年齡的增長(zhǎng)，精子的DNA會(huì)發(fā)生什么變化呢?

DNA stands for deoxyribonucleic acid, and it's the familiar "double helix" molecule forming the building blocks of every living organism. In our body, DNA is tightly coiled up into chromosomes, and each chromosome contains a specific number of genes. In every cell in our body, we have 23 pairs of chromosomes.

DNA代表脫氧核糖核酸，它是一種常見(jiàn)的“雙螺旋”分子，構(gòu)成了每一個(gè)生物體的組成部分。在我們的身體里，DNA緊緊地纏繞成染色體，每條染色體都含有特定數(shù)量的基因。在我們身體的每個(gè)細(xì)胞中，我們有23對(duì)染色體。

An example of this that many people are familiar with is Down syndrome, which means the individual was born with three copies of chromosome 21 – creating more than 23 chromosomes. Interestingly, there is no paternal age effect with Down syndrome, yet there's twice the increased risk of miscarriage with advanced paternity.

很多人都熟悉的一個(gè)例子是唐氏綜合癥，這意味著一個(gè)人出生時(shí)攜帶著3個(gè)21號(hào)染色體副本——產(chǎn)生了23條以上的染色體。有趣的是，父親的年齡對(duì)唐氏綜合癥沒(méi)有影響，但父親的年齡越長(zhǎng)，流產(chǎn)的風(fēng)險(xiǎn)就會(huì)增加一倍。

Additionally, as men age, there's a higher chance of their children developing single gene disorders such as achondroplasia and osteogenesis imperfecta. Achondroplasia is a genetic disorder that arises from a point mutation in the FGFR3 gene and results in dwarfism.

此外，隨著男性年齡的增長(zhǎng)，他們的孩子更有可能患上單基因疾病，如軟骨發(fā)育不全和成骨不全。軟骨發(fā)育不全是由FGFR3基因點(diǎn)突變引起的一種遺傳性疾病，可導(dǎo)致侏儒癥。

Population geneticist, James Crow, claimed: "The greatest mutational health hazard to the human genome is fertile older males." Researchers sequenced the whole genome of 78 Icelandic parent-offspring trios of children with autism and found it is the age of the father that is the dominant factor in determining the number of new mutations in the child.

人口遺傳學(xué)家詹姆斯·克勞(James Crow)聲稱:“對(duì)人類基因組最大的突變健康危害是生育能力較強(qiáng)的老年男性。”研究人員對(duì)78名冰島自閉癥兒童的父母和子女進(jìn)行了全基因組測(cè)序，發(fā)現(xiàn)父親的年齡是決定孩子新突變數(shù)量的主要因素。

The study was published in the journal Nature and showed paternal contribution of two additional mutations per year. The sperm could be the source of evolution .

這項(xiàng)研究發(fā)表在《自然》(Nature)雜志上，顯示父親每年會(huì)增加兩種基因突變。精子可能是進(jìn)化的來(lái)源。

Nevertheless, there are social benefits and detriments of older paternity. Later age at parenthood is also associated with a more emotionally and financially stable family environment. On the contrary, there is a risk of the father dying before the child becomes an adult.

然而，年長(zhǎng)的父親既有社會(huì)益處，也有壞處。晚年為人父母也與更穩(wěn)定的情感和財(cái)務(wù)狀況有關(guān)。相反，在孩子成年之前，有父親死亡的風(fēng)險(xiǎn)。

In summary, "advanced paternal age" is generally used to describe men age 40 and older at the time of conception. However, there is no uniformly accepted definition. The effects of reproductive aging on sperm DNA are more gradual and complex. Also, we don’t have diagnostic tests to identify when a man's sperm might be damaged due to aging. And there's not enough data on the genetic effects related to freezing and thawing sperm to recommend young men to bank their sperm, either. Perhaps this is something to consider in the future.

總而言之，“高齡父親”一般用于描述40歲以上男性在受孕時(shí)的年齡。然而，并沒(méi)有統(tǒng)一的定義。生殖老化對(duì)精子DNA的影響更為緩慢和復(fù)雜。此外，我們還沒(méi)有診斷測(cè)試來(lái)確定男性的精子何時(shí)可能因衰老而受損。而且，關(guān)于冷凍和解凍精子的遺傳效應(yīng)，也沒(méi)有足夠的數(shù)據(jù)來(lái)建議年輕男性將精子儲(chǔ)存起來(lái)。也許這是將來(lái)要考慮的事情。